Previously, a radioimmunoassay method was developed to study the distribution of met5-enkephalin-arg6-phe7 (ME-arg-phe) in the brain and this opioid heptapeptide was found to be most concentrated in striatum. In this study, the interaction between ME-arg-phe and dopamine in striatum was studied. Chronic treatment of rats with haloperidol elevated the ME-arg-phe content in striatum but not in other regions. Following inhibition of the ME-arg-phe degradation by captopril, the accumulation rate of ME-arg-phe was greater in haloperidol treated rats than in control rats. The results suggest that haloperidol, a dopamine receptor blocker, increases ME-arg-phe biosynthesis. Previously, it was found that chronic haloperidol treatment also increased the content of met5-enkephalin (ME). In view of the fact that ME and ME-arg-phe are derived from the same precursor, preproenkephalin A, it is suggested that chronic haloperidol treatment enhances the preproenkephalin A biosynthesis. Cardioexcitatory neuropeptide, phe-met-arg-phe-NH2 (FMRF-NH2) was originally isolated from ganlia of macrocallista mimbosa and subsequently existence of EMRF-NH2-like immunoreactivity in rat CNS was reported. Because of its structural similarity to ME-arg-phe, the distribution and biological activity of the FMRF-NH2 immunoreactive material in CNS was studied. In rat brain and spinal cord, FMRF-NH2-like immunoreactivity is unevenly distributed. The highest content is in hypothalamus and the lowest in cerebellu. In spinal cord, FMRF-NH2 immunoreactivity is higher in dorsal horn. Biochemical analysis of the FMRF-NH2 like material revealed that endogenous FMRF-NH2 like material is similar to but not identical to authentic FMRF-NH2. Because of this, endogenous FMRF-NH2 material was partially purified and biological property tested. The endogenous FMRF-NH2 like material was found to reduce the analgesic effect of ME-arg-phe when injected intrathecally. The function of FMRF-NH2 like material will be further studied.